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Biomedical subjects

S Rasheed

Publications and source records attributed to S Rasheed.

At least 73 records · Page 4Linked to original sources
PubMed1987

Immunohistology of persistent generalized lymphadenopathy. Evidence for progressive lymph node abnormalities in some patients.

Immunohistologic analysis of cellular changes in serial lymph node biopsies of eight patients with persistent generalized lymphadenopathy (PGL) syndrome was performed and correlated with clinical and laboratory findings to better determine the natural history of human immunodeficiency virus (HIV) infection. The authors observed decreased follicle size and area in the second biopsies of six of the eight patients, associated in some with increased numbers of B-cells in medullary regions (four of eight) and more involuted follicles (four of eight). Five cases showed progressively increased paracortical areas in the second biopsies, with increased numbers of T-cytotoxic/suppressor cells and decreased T-helper cells. Seven of the patients also had a progressive loss of T-helper cells in the peripheral blood. These findings provide tissue and peripheral blood evidence for progressive immunologic deterioration in some patients with PGL.

AIDS-Related Complex↗
PubMed1987

AIDS-related malignant lymphoma: results of prospective treatment trials.

Twenty-two consecutive patients with high-grade, B-cell lymphomas related to the acquired immunodeficiency syndrome (AIDS) were accrued onto two sequential phase II studies, consisting of a standard regimen (M-BACOD, group no. 1, N = 13), or a novel, intensive regimen (group no. 2, N = 9), which included high-dose cytosine arabinoside (HD-Ara-C), and high-dose methotrexate (HD-MTX), in an attempt to prevent CNS relapse and improve response rates. Stage IV disease was present in 82%. Complete remission (CR) was achieved in seven of 13 patients (54%) in group no. 1, and in three of nine (33%) group no. 2 (P = NS). By multivariate analysis, the most significant factor in predicting response was a Karnofsky performance score (KPS) greater than 60 (P = .04). Three of the ten patients who achieved CR on either regimen have relapsed; in all, five of 13 patients (31%) in group no. 1 have achieved disease-free survival for more than 1 year, compared with one of nine (11%) in group no. 2. CNS progression occurred in six patients in group no. 2, and in two patients in group no. 1. Hematologic toxicity was significantly greater in group no. 2, and these patients had an increased risk of opportunistic infection (one in group no. 1 v seven in group no. 2; P less than .01). Survival was similar, with a median of 11 months in group no. 1 and 6 months in group no. 2. We conclude that the intensive regimen of combination chemotherapy described here is associated with significant risk of early death due to opportunistic infection in patients with AIDS-related lymphoma, and that progression in the CNS remains a major problem. Trials of combination chemotherapy of a less intensive nature, perhaps in combination with immunomodulators or antiretroviral agents should be explored.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human normal and tumor cell lines: comparison of fibronectins and collagens.

Human tumor cell lines, a rhabdomyosarcoma (RD), and a fibrosarcoma (HT-1080) were distinguished from normal human fibroblasts by tumorigenicity in athymic nude mice and immunosuppressed rats and hamsters, secretion of different types of collagen and procollagen molecules, and reduced amounts of fibronectin. The fibronectins secreted by both normal and tumor cells did not show any significant structural difference and were phosphorylated only on serine residue(s). However, fibronectin secreted by the tumor cells exhibited decreased electrophoretic mobility and was associated with as yet unidentified phosphorylated macromolecules.

Animals↗
PubMed1986

Cell killing by ultraviolet-inactivated human immunodeficiency virus.

Extensive cell killing and cytopathology were observed within 24 hr after exposure of a clonal cell line of human T-4 lymphocytes (RH9) to culture supernatants containing human immunodeficiency virus (HIV). Ultraviolet-irradiated HIV-containing culture fluids were also capable of killing RH9 cells and of inducing specific cytopathic effects which were indistinguishable from those induced by unirradiated virus-containing preparations. The uv-irradiated HIV was incapable of forming proviral DNA using the endogenous virion genomic RNA as a template. The RH9 cells persistently infected with HIV did not release soluble cytotoxic factors to account for the cell killing observed when culture supernatants were added to uninfected RH9 cells. The fraction involved in cell killing had the hydrodynamic properties of a retrovirus. These results suggest that a virion component is responsible for cell killing by HIV.

Cell Line↗
PubMed1986

Virus-neutralizing activity, serologic heterogeneity, and retrovirus isolation from homosexual men in the Los Angeles area.

Human retroviruses have been causally associated with the development of the acquired immune deficiency syndrome (AIDS) in groups of individuals at high risk including intravenous drug users, hemophiliacs, and homosexual men. Aside from classic AIDS, homosexual men also develop persistent generalized lymphadenopathy (PGL) which is considered a part of the AIDS-related complex (ARC). We have isolated 70 strains of retroviruses related to human T-lymphotropic viruses type III (HTLV-III) from patients with PGL, AIDS, or ARC. analyses of sera from these patients indicated a high degree of serologic heterogeneity in the antibody titers and their reactivities toward various HTLV-III viral proteins. In addition, we have detected virus-neutralizing antibodies in approximately 50% of the serum samples tested from patients with PGL or AIDS. This is the first comprehensive virologic and serologic report on more than 100 patients studied at one institution in Los Angeles.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Localization of the feline sarcoma virus fgr gene product (P70gag-actin-fgr): association with the plasma membrane and detergent-insoluble matrix.

The v-fgr oncogene codes for a unique transforming protein (P70gag-actin-fgr) that contains virus-specific determinants and cell-derived sequences for both a tyrosine-specific kinase domain and an actin domain. We examined the subcellular distribution of the v-fgr protein by immunofluorescence microscopy and various cell fractionation techniques. By immunofluorescence, the v-fgr protein was localized in a diffuse cytoplasmic pattern within transformed cells. The v-fgr protein was not detectable at substratum adhesion sites. Crude membrane preparations (P100) obtained from fgr-transformed cells contained elevated levels of P70gag-actin-fgr. Further analysis of membranes on discontinous sucrose gradients revealed that P70gag-actin-fgr cofractionated with plasma membranes. Using an alternate method of fractionation, we found that the majority of the v-fgr protein remained with the insoluble matrix obtained by treating cells with a buffer containing Triton X-100. When membranes were similarly treated with detergent, nearly all of v-fgr protein remained with the residual insoluble matrix. These results suggest that the transforming activity of P70gag-actin-fgr may be directed to subcellular cytoskeletal targets at or near the cytoplasmic face of the plasma membrane.

Actins↗
PubMed1986

Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results.

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Human T-cell lymphotropic virus type III associated disorders. The spectrum in the heterosexual population.

Eleven heterosexual patients (nine women, two men) without classic risk factors for development of acquired immunodeficiency syndrome (AIDS) were seen between March 1983, and April 1985, and diagnosed as having AIDS (four), persistent, generalized lymphadenopathy (PGL) (four), or asymptomatic human T-cell lymphotropic virus type III (HTLV-III) carrier state (three). The clinical presentations and course of those with AIDS or PGL were similar to those reported in homosexual men with AIDS or PGL, with reversed T4/T8 ratio, and the presence of antibody to HTLV-III. Asymptomatic carriers had normal T4/T8 ratios, had an absence of HTLV-III antibodies, but had HTLV-III virus cultured from blood. We conclude that the heterosexual population, with or without history of sexual exposure to individuals at risk for AIDS, may develop a wide range of clinical manifestations secondary to HTLV-III, varying from AIDS to the asymptomatic carrier state.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Rectal lymphoma in homosexual men.

Lymphoma of the rectum is a rare tumor and in most studies is not separated from other lymphomas of the large intestine. We have recently examined four homosexual men with lymphoma presenting in the rectum. Symptoms included rectal bleeding in three, pain on defecation in two, and mucoid rectal discharge in two. Systemic "B" symptoms (ie, fever, night sweats, and/or weight loss), as well as a rectal mass, were present in all four. All were high-grade tumors, with B-cell immunoblastic sarcoma in two and small noncleaved Burkitt-like lymphoma in two. Intracytoplasmic immunoperoxidase staining revealed monoclonal kappa light chains in three tumors, whereas the fourth was nonstaining. Immunologic abnormalities were similar to those reported in patients with acquired immunodeficiency syndrome. Antibodies to human T-cell lymphotropic virus type III were found in the three cases tested, and retrovirus was cultured from lymphomatous tissue in one. Despite multiagent chemotherapy, two patients died within six months of diagnosis and a third has recently suffered relapse within the central nervous system.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Retrovirus and malignant lymphoma in homosexual men.

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Characterization of tumor cell lines from a spontaneous rat sarcoma expressing an endogenous retrovirus.

We have characterized various biologic, immunologic and growth properties of several cell lines established from a spontaneous rat sarcoma that was discovered more than 60 yr ago. The tumors consisted of mixed cell types with no detectable host cellular immune response. Cultures derived from single-cell clones of the parental cell line were non-invasive but highly tumorigenic even in adult rats. The cultured cells spontaneously released replication-competent endogenous rat type C virus which did not carry a transforming gene in its genome. Since normal cells from the same rat strain did not produce a retrovirus, it is possible that production of the endogenous retrovirus may have triggered specific cellular changes necessary for the oncogene expression and development of this tumor.

Animals↗
PubMed1983

Isolation and characterization of new ecotropic murine leukemia viruses after passage of an amphotropic virus in NIH Swiss mice.

Amphotropic murine leukemia viruses (MuLV-A) cause mainly lymphoma in newborn inoculated NIH Swiss mice after a long latent period of 6-12 months. Rarely, however, about 1% of the inoculated mice develop hind limb paralysis and progressive central nervous system disease. The biological properties and RNase T1-resistant oligonucleotide fingerprints of the recovered viruses from tissues of both lymphomatous and paralyzed mice inoculated with MuLV-A were analyzed. These results indicate that serial in vivo passages of MuLV-A in NIH Swiss mice lead to generation of new MuLVs of both amphotropic and ecotropic host ranges. The recovered amphotropic viruses are highly lymphomagenic and are recombinants of MuLV-A-specific oligonucleotides and endogenous mouse sequences. The ecotropic viruses fall into two groups: (1) recombinants of MuLV-A genes and NIH Swiss mouse viral or cellular sequences and (2) new ecotropic viruses with oligonucleotide fingerprints not related to any of the known MuLVs. The naturally occurring ecotropic MuLVs of the wild mice produce both lymphoma and paralysis in NIH Swiss mice. The viruses recovered from in vivo passages are mainly of ecotropic host range although dual-tropic virus activity is occasionally seen in the spleens but not in the brains or spinal cords of the lymphomatous or paralyzed mice. Oligonucleotide fingerprinting of the recovered MuLV-Es from paralyzed mice are identical to the input MuLV-Es, indicating that the parental MuLV-E alone, without recombination, is responsible for the paralytic disease.

Animals↗
PubMed1983

Nucleotide sequence of the Rasheed rat sarcoma virus oncogene: new mutations.

The nucleotide sequence of the oncogene of the Rasheed strain of rat sarcoma virus was determined. The oncogene (Ra-v-ras) encodes a 29,000-dalton (p29) transforming protein. This protein is distinct from the immunologically related 21,000-dalton protein (p21) of the Harvey murine sarcoma virus in its amino terminus and in having additional mutations in its carboxyl terminus. Although the functional significance of these changes is unknown, they appear to occur only in rat sarcoma virus.

Amino Acid Sequence↗
PubMed1983

Resistance to fibroblasts and hematopoietic cells to ecotropic murine leukemia virus infection; an Akvr-1R gene effect.

A gene named Akvr-1 segregates as a dominant allele in California wild mice (LC). Unlike Fv-1 and Fv-2 restriction alleles, the Akvr-1 confers resistance to replication of all ecotropic (N-, B-, and NB-tropic) murine leukemia viruses (MuLV-E) and prevents endogenous AKR virus-induced lymphoma/leukemia in F1 hybrids of AKR x LC. We have tested fibroblasts and hematopoietic cells from mice of defined Akvr-1 genotypes for in vitro susceptibility to various MuLV infections. Our results indicated a dominant in vitro resistance of exogenously MuLV-E infected cells carrying Akvr-1R allele although resistance was stronger in the homozygous cells than in the heterozygous cells. Moreover, resistance of cells to virus replication was not abrogated by high multiplicities of infection or by growth stimulation of hematopoietic cultures by various T- or B-cell-responsive mitogenic agents.

Animals↗
PubMed1983

Feline oncornavirus-associated cell membrane antigen: a viral and not a cellularly coded transformation-specific antigen of cat lymphomas.

The feline oncornavirus-associated cell membrane antigen (FOCMA) was defined as a tumor antigen common to cat lymphomas and fibrosarcomas induced by feline leukemia virus (FeLV) and feline sarcoma virus (FeSV), respectively. The antigen was recognized by sera from cats thought to be resistant to leukemogenesis. We report here that a common denominator in the activity of naturally occurring viremic cat antisera to FOCMA is, in fact, their reactivity to FeLV C antigenic determinants. The cat antisera, monoclonal antibodies to FOCMA, and monoclonal antibodies to FeLV C, all reacted in immunofluorescence assays with FeLV C-infected cells and immunoprecipitated a molecule electrophoretically indistinguishable from envelope glycoprotein of FeLV. Viremic cat antisera to FOCMA bound to budding virus particles of FeLV C-infected cells, even though some of them could not be absorbed by mature virion proteins. Thus, the unusual feature of cat antibodies to FOCMA is their binding to nascent but not to mature virus particles. FOCMA-positive cat lymphomas expressed antigenic determinants of FeLV-C gp70, with or without productive infection. FeLV-negative tumors not expressing FeLV C gp70 were also FOCMA negative. Furthermore, most of the viremic cat sera and the monoclonal antibodies to FOCMA did not react with FeSV-transformed nonproducer cells. The absence of FOCMA from these cells and from FeLV-negative lymphoid tumors and its presence in FeLV-C infected fibroblasts indicated that this antigen is virus encoded and not a cellular tumor-specific antigen.

Animals↗
PubMed1983

Molecular cloning of integrated Gardner-Rasheed feline sarcoma virus: genetic structure of its cell-derived sequence differs from that of other tyrosine kinase-coding onc genes.

Gardner-Rasheed feline sarcoma virus (GR-FeSV) is an acute transforming retrovirus which encodes a gag-onc polyprotein possessing an associated tyrosine kinase activity. The integrated form of this virus, isolated in the Charon 21A strain of bacteriophage lambda, demonstrated an ability to transform NIH/3T3 cells at high efficiency upon transfection. Foci induced by GR-FeSV DNA contained rescuable sarcoma virus and expressed GR-P70, the major GR-FeSV translational product. The localization of long-terminal repeats within the DNA clone made it possible to establish the length of the GR-FeSV provirus as 4.6 kilobase pairs. The analysis of heteroduplexes formed between lambda feline leukemia virus (FeLV) and lambda GR-FeSV DNAs revealed the presence of a 1,700-base-pair FeLV unrelated segment, designated v-fgr, within the GR-FeSV genome. The size of this region was sufficient to encode a protein of approximately 68,000 daltons and was localized immediately downstream of the FeLV gag gene coding sequences present in GR-FeSV. Thus, it is likely that this 1.7-kilobase-pair stretch encodes the onc moiety of GR-P70. Utilizing probes representing v-fgr, we detected homologous sequences in the DNAs of diverse vertebrate species, implying that v-fgr originated from a well-conserved cellular gene. The number of cellular DNA fragments hybridized by v-fgr-derived probes indicated either that proto-fgr is distributed over a very large region of cellular DNA or represents a family of related genes. By molecular hybridization, v-fgr was not directly related to the onc genes of other known retroviruses having associated tyrosine kinase activity.

Animals↗
PubMed1983

Inherited susceptibility to retrovirus-induced transformation of Gardner syndrome cells.

Skin fibroblasts from patients with Gardner syndrome (GS), those with familial polyposis coli (FPC), and spouse or unrelated controls were karyotyped and tested for various growth properties including susceptibility to transformation by viral or chemical agents. Our results indicated that based on the higher susceptibility to retrovirus-induced transformation and chromosomal aneuploidy, the GS and FPC cells could be distinguished from those of the general population with more than 70% accuracy. However, much work is in order before any biological assay can be used for clinical diagnosis of GS or FPC patients.

Aneuploidy↗